Mapping Regional Homogeneity and Functional Connectivity of the Visual Cortex in Resting-State fMRI.

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, has been used to evaluate synchronous neuronal activity changes in retinitis pigmentosa (RP). The purpose of this study is to describe our method for analysis of intra- and interregional synchronizations of changes in neuronal activity in RP patients. The advantages of the combined ReHo and FC method are that it is both noninvasive and sufficiently sensitive to investigate changes in cerebral synchronous neuronal activity changes in vivo. Here, 16 RP patients and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. Two sample t-tests were conducted to compare ReHo and FC across groups. Our results showed that visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream occurred in the RP patients. Here, we describe the details of this method, its use, and the impact of its key parameters in a step-by-step manner.

Altered Temporal Dynamic Intrinsic Brain Activity in Late Blindness.

Previous neuroimaging studies demonstrated that visual deprivation triggers significant crossmodal plasticity in the functional and structural architecture of the brain. However, prior neuroimaging studies focused on the static brain activity in blindness. It remains unknown whether alterations of dynamic intrinsic brain activity occur in late blindness (LB). This study investigated dynamic intrinsic brain activity changes in individuals with late blindness by assessing the dynamic amplitude of low-frequency fluctuations (dALFFs) using sliding-window analyses. Forty-one cases of late blindness (LB) (29 males and 12 females, mean age: 39.70 ± 12.66 years) and 48 sighted controls (SCs) (17 males and 31 females, mean age: 43.23 ± 13.40 years) closely matched in age, sex, and education level were enrolled in this study. The dALFF with sliding-window analyses was used to compare the difference in dynamic intrinsic brain activity between the two groups. Compared with SCs, individuals with LB exhibited significantly lower dALFF values in the bilateral lingual gyrus (LING)/calcarine (CAL) and left thalamus (THA). LB cases also showed considerably decreased dFC values between the bilateral LING/CAL and the left middle frontal gyrus (MFG) and between the left THA and the right LING/cerebelum_6 (CER) (two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05). Our study demonstrated that LB individuals showed lower-temporal variability of dALFF in the visual cortices and thalamus, suggesting lower flexibility of visual thalamocortical activity, which might reflect impaired visual processing in LB individuals. These findings indicate that abnormal dynamic intrinsic brain activity might be involved in the neurophysiological mechanisms of LB.

Large-Scale Neuronal Network Dysfunction in Diabetic Retinopathy.

Diabetic retinopathy (DR) patients are at an increased risk of cognitive decline and dementia. There is accumulating evidence that specific functional and structural architecture changes in the brain are related to cognitive impairment in DR patients. However, little is known regarding whether the functional architecture of resting-state networks (RSNs) changes in DR patients. The purpose of this study was to investigate the intranetwork functional connectivity (FC) and functional network connectivity (FNC) of RSN changes in DR patients using independent component analysis (ICA). Thirty-four DR patients (18 men and 16 women; mean age, 53.53 ± 8.67 years) and 38 nondiabetic healthy controls (HCs) (15 men and 23 women; mean age, 48.63 ± 11.83 years), closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. ICA was applied to extract the nine RSNs. Then, two-sample t-tests were conducted to investigate different intranetwork FCs within nine RSNs between the two groups. The FNC toolbox was used to assess interactions among RSNs. Pearson correlation analysis was conducted to explore the relationship between intranetwork FCs and clinical variables in the DR group. A receiver operating characteristic (ROC) curve was conducted to assess the ability of the intranetwork FCs of RSNs in discriminating between the two groups. Compared to the HC group, DR patients showed significant decreased intranetwork FCs within the basal ganglia network (BGN), visual network (VN), ventral default mode network (vDMN), right executive control network (rECN), salience network (SN), left executive control network (lECN), auditory network (AN), and dorsal default mode network (dDMN). In addition, FNC analysis showed increased VN-BGN, VN-vDMN, VN-dDMN, vDMN-lECN, SN-BGN, lECN-dDMN, and AN-BGN FNCs in the DR group, relative to the HC group. Furthermore, altered intranetwork FCs of RSNs were significantly correlated with the glycosylated hemoglobin (HbA1c) level in DR patients. A ROC curve showed that these specific intranetwork FCs of RSNs discriminated between the two groups with a high degree of sensitivity and specificity. Our study highlighted that DR patients had widespread deficits in both low-level perceptual and higher-order cognitive networks. Our results offer important insights into the neural mechanisms of visual loss and cognitive decline in DR patients.

Disrupted topological organization of human brain connectome in diabetic retinopathy patients.

OBJECTIVE: There is increasing neuroimaging evidence that type 2 diabetes patients with retinal microvascular complications show abnormal brain functional and structural architecture and are at an increased risk of cognitive decline and dementia. However, changes in the topological properties of the functional brain connectome in diabetic retinopathy (DR) patients remain unknown. The aim of this study was to explore the topological organization of the brain connectome in DR patients using graph theory approaches. METHODS: Thirty-five DR patients (18 males and 17 females) and 38 healthy controls (HCs) (18 males and 20 females), matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of brain functional connectome at both global and nodal levels. RESULTS: Both DR and HC groups showed high-efficiency small-world network in their brain functional networks. Notably, the DR group showed reduction in the clustering coefficient (P=0.0572) and local efficiency (P=0.0151). Furthermore, the DR group showed reduced nodal centralities in the default-mode network (DMN) and increased nodal centralities in the visual network (VN) (P<0.01, Bonferroni-corrected). The DR group also showed abnormal functional connections among the VN, DMN, salience network (SN), and sensorimotor network (SMN). Altered network metrics and nodal centralities were significantly correlated with visual acuity and fasting blood glucose level in DR patients. CONCLUSION: DR patients showed abnormal topological organization of the human brain connectome. Specifically, the DR group showed reduction in the clustering coefficient and local efficiency, relative to HC group. Abnormal nodal centralities and functional disconnections were mainly located in the DMN, VN, SN, and SMN in DR patients. Furthermore, the disrupted topological attributes showed correlations with clinical variables. These findings offer important insight into the neural mechanism of visual loss and cognitive deficits in DR patients.

Altered intra- and inter-regional functional connectivity of the visual cortex in individuals with peripheral vision loss due to retinitis pigmentosa.

This study investigated changes in intra- and inter-regional functional connectivity (FC) in individuals with retinitis pigmentosa (RP) by using regional homogeneity (ReHo) and FC methods. Sixteen RP individuals and 14 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans (fMRI). A combined ReHo and FC method was conducted to evaluate synchronization of brain activity. Compared with HCs, RP individuals had significantly lower ReHo values in the bilateral lingual gyrus/cerebellum posterior lobe (LGG/CPL). In FC analysis, the RP group showed decreased positive FC relative to the HC group, from bilateral LGG/CPL to bilateral LGG/cuneus (CUN) and to left postcentral gyrus (PosCG). In contrast, the RP group showed increased negative FC relative to the HC group, from bilateral LGG/CPL to bilateral thalamus, and decreased negative FC from bilateral LGG/CPL to right middle frontal gyrus (MFG), and to left inferior parietal lobule (IPL). Moreover, ReHo values of the bilateral LGG/CPL showed negative correlations with the duration of RP. FC values of the bilateral LGG/CPL-left IPL showed negative correlations with best-corrected visual acuity (BCVA) of the right eye and left eye in RP individuals. Our results reveal reduced synchronicity of neural activity changes in the primary visual area in RP individuals. Moreover, RP individuals showed intrinsic visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream, suggesting impaired visuospatial and stereoscopic vision.

Abnormal intrinsic functional network hubs and connectivity following peripheral visual loss because of inherited retinal degeneration.

Previous neuroimaging studies have shown that the long-term effects of peripheral vision loss lead to functional and morphological reorganization in visual cortices. However, it has not been determined whether whole-brain functional network centrality changes occur during peripheral vision loss. This study aimed to investigate functional network centrality and connectivity changes in individuals with peripheral vision loss because of retinitis pigmentosa (RP) by using voxel-wise degree centrality (DC) and seed-based resting-state functional connectivity (rsFC) methods. In total, 30 RP patients (18 men and 12 women, mean age: 38.77±14.44 years) and 30 healthy controls (HCs) (18 men and 12 women, mean age: 34.57±10.70 years) matched for age, sex, cognition, education, and visual expertise underwent resting-state magnetic resonance imaging scans. Graph theory-based network analysis was carried out to investigate DC between the two groups. A seed-based rsFC analysis was then carried out to further reveal the abnormal functional connectivity of the altered DC brain region. Pearson's correlation was used to analyze the relationships of DC and rsFC index with the clinical variables in RP patients: visual function (best-corrected visual acuity and visual field, VF) and optical coherence tomography testing (mean retinal nerve fiber layer). Compared with HCs, RP patients had significantly lower DC values in the bilateral cuneus/calcarine/precuneus (CUN/CAL/PreCUN) [Brodmann's area (BA) 17/18/19/30/31]. In addition, RP patients showed decreased rsFC index, relative to that of HCs, from bilateral CUN/CAL/PreCUN to bilateral lingual/cuneus/calcarine (LIG/CUN/CAL) (BA 18/19/30) and the bilateral postcentral gyrus/superior parietal lobule (BA 3/5/7/40). In contrast, RP patients showed increased rsFC index, relative to that of HCs, from bilateral CUN/CAL/PreCUN to bilateral thalamus/caudate (voxel-level P<0.01; Gaussian random-field correction, cluster-level P<0.05). Moreover, the course of RP showed a negative correlation with the mean DC values of the bilateral CUN/CAL/PreCUN (r=-0.480; P=0.007) and the mean FC values of the bilateral LIG/CUN/CAL (r=-0.484; P=0.007); the mean DC values of the bilateral CUN/CAL/PreCUN in RP showed a negative correlation with the right eye VF (r=-0.411; P=0.024) and left eye VF (r=-0.426; P=0.019). Our results showed that RP patients showed abnormal function network hubs in various brain regions related to visual, thalamocortical, and sensorimotor networks; these might reflect impaired top-down modulations, visual imagery, and visuomotor coordination in RP patients. Moreover, the DC index can be used as a biomarker to indicate the severity of visual loss in RP patients.

Altered functional connectivity of primary visual cortex in late blindness.

BACKGROUND: Previous studies demonstrated that early blindness is associated with abnormal intrinsic functional connectivity (FC) between the primary visual cortex (V1) and other sensory areas. However, the V1 pattern of spontaneous neural activity occurring in late blindness (LB) remains unknown. The purpose of this study was to investigate the intrinsic FC patterns of V1 in LB. MATERIALS AND METHODS: Thirty LB individuals (18 males and 12 females; mean age: 38.76±14.43 years) and 30 sighted controls (SCs) individuals (18 males and 12 females; mean age: 38.67±13.85 years) closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Region of interest analysis was performed to extract the correlation coefficient matrix among each pair of Brodmann area (BA) 17 and FC between V1 and vision-related subcortical nuclei. RESULTS: Compared with SCs, LB individuals showed a decreased FC between the left V1 and the bilateral cuneus (CUN)/lingual gyrus (LGG)/calcarine (CAL) (BA 18/19/30) and left precentral gyrus (PreCG) and the postcentral gyrus (PostCG) (BA 2/3/4). Also, LB individuals showed a decreased FC between the right V1 and the bilateral CUN/LGG/CAL (BA 18/19/30) and the left PreCG and PostCG (BA 2/3/4/6) (voxel-level: P<0.01, cluster-level: P<0.05). Meanwhile, LB individuals showed a decreased FC between the left V1 and the right V1 and increased FC between the left V1 and the right superior colliculus, the right V1, and the left hippocampus (P<0.05). Moreover, a positive correlation was observed between the onset age of blindness and FC values in V1 to CUN/LGG/CAL in LB. CONCLUSION: Our results highlighted that LB induces a decreased FC between V1 and higher visual areas, motor cortices, and somatosensory cortices at rest. This might indicate that LB humans could present with impaired top-down modulations, visual imagery, and vision-motor function.

Abnormal intrinsic brain activity in individuals with peripheral vision loss because of retinitis pigmentosa using amplitude of low-frequency fluctuations.

The study aimed to determine alterations in intrinsic brain activity in retinitis pigmentosa (RP) individuals using the amplitude of low-frequency fluctuation (ALFF)/fractional amplitude of low-frequency fluctuation (fALFF) method. Sixteen RP individuals (10 men and six women) and 14 healthy controls (HCs) (six men and eight women) closely matched in age, sex, and education were enrolled in the study. The ALFF/fALFF method was applied to compare different intrinsic brain activities between the RP group and the HC group. The relationship between the mean ALFF/fALFF signal values of different brain regions and the visual measurements in RP group was analyzed by Pearson correlation. Compared with HCs, RP individuals had significantly lower ALFF values in the bilateral lingual gyrus (LIGG)/cerebellum posterior lobe [Brodmann area (BA) 17,18], but lower fALFF values in the bilateral LIGG/cerebellum anterior lobe (BA 17,18). Meanwhile, RP individuals had significantly higher ALFF in the bilateral precuneus cortex/middle cingulate cortex (BA 7,31), as well as higher fALFF values in the left superior/middle frontal gyrus (BA 9,10) and bilateral supplementary motor area (BA 6,8) (voxel-level P<0.01, cluster-level P<0.05). Moreover, the fALFF values of the bilateral LIGG/cerebellum anterior lobe showed positive relationships with the best-corrected visual acuity (BCVA)-oculus dexter (r=0.574, P=0.020) and BCVA-oculus sinister (r=0.570, P=0.021) in RP individuals; our results provide evidence that RP individuals may have impaired intrinsic brain activity in the primary visual area and the visuomotor coordination area that correlates with BCVA. Moreover, our findings indicate that reorganization of the dorsal visual stream and the parietoprefrontal pathway occurs in RP individuals.